Therapeutical preparation



Patented Nov. 14, 1933 PATENT orrics THERAPEUTICAL PREPARATION Maxwell M. Becker, Kansas City, Mo., assignor to George A. Breon and Company,

Incorporated, Kansas City, Mo., a corporation of Missouri No Drawing. Application July 25,1932 Serial No. 624,659

4 Claims.

This invention relates to therapeutical preparations, and with regard to certain more specific features, to therapeutical fluids for parenteral injection in connection with the treatment known I as non-specific protein therapy.

' Among the several objects of the invention may be noted the provision of a therapeutical preparation of the class indicated which combines lacteal proteins, in concentrated form, with certain colloidally dispersed metals, thereby to secure new and advantageous results in nonspecific protein therapy; the provision of a prep,- aration of the class described which is aseptic;

the provision of a preparation of the class described which is so constituted as to be effective in volumes considerably less than those heretofore injected, thereby tending greatly to reduce the pain of the subject due to distension of the tissues by bulkyfiuids and thereby also. making it' possible to utilize, for injection, muscles or tissues that would not otherwise be available; the

' sequence of steps, and features of composition and synthesis, which will be -exemplified in the products and processes hereinafter described, and the scope of the application of which will be indicated in the following claims.

Milk, usually from the cow, has heretofore been successfully injected parenterally in man and other animals for the purpose of stimulating resistance, on the part of the body, to infective diseases. This treatment is often referred to as non-specific protein therapy. butyrate, a metallic colloid, has also been injected to obtain similar effects. It is the primary object.

of the present invention to combine and hold in stable solution the concentrated milk derivatives or lacteal proteins and metallic colloids of these general types, for the purpose of increasing the therapeutical emciency of the treatment.

The invention is brought about in the following manner:

Lacteal proteins are first rendered soluble, preferably by the action of either ahydrate or a Manganese phosphate (sodium tri-basic phosphate. being specifically preferred). The lacteal proteins used are generally those obtained from powdered, skimmed cow's milk, although other milks, such as goats milk, or even human milk, are not to be considered as excluded. To the proteins thus made soluble, an agent is added which prevents the subsequent precipitation of the proteins in a solution either slightly acid or slightly alkaline, or neutral. Alkaline citrates, such as sodium citrate, are successful as such agents. The alkaline citrate has the additional advantage of holding in solution any phosphates left therein during the process of manufacture.

For exampl a mixture 'the following proportions:

Powdered skimmed milk 200 grams Sodium tri-basic phosphate, C. P.-- 100 grams Distilled water 1200 cubic centimeters This mixture. is heated, say inia Pyrex" boil- 7s ing fiask, at a temperature of the order of to C., for about 100 minutes, the flask being occasionally shaken. The hot mixture is then filtered through rapidly-acting funnels and filter paper of relatively fine grain. The resulting filtrate has a gravity of about 9 /2 Baum at 25 C. It is then evaporated in a porcelain evaporating dish on a water bath at a temperature. of

'the order of 75 to 80 C., until concentrated to erably through very porous fiber paper and a funnel of the Buchner type. The filtrate is then refrigerated at the order of 6 C. for three days or more, at the end of which any accumulated sediment is removed.

The clear liquid prepared in the manner described contains approximately 0.08 grams of protein per cubic centimeter.

This concentrated protein solution is now com- 5v bined with the metallic colloid,for example manganese butyrate, in the following man ner (the amounts being given as those required for I solution) one cubiccentimeter of finished is completely 10.

' 0.045 grams of sodium citrate is made according to 70 l flodium citrate nee rev dissolved in 0.15 cubic centimeters of distilled water. To solution is now added 0.5 cubic centimeters of the protein solution prepared in the foregoing manner. The solution is then acidulated with 0.012 cubic centimeters of butyric acid (C. P.) which is added in small portions and with thorough mixing after each addition. To the acidulated solution is then added in small quantities 0.3 cubic centimeters of a 5% solution oi manganese butyrate, containing a small proportion of benzyl alcohol, and again with thorough a w after each addition Additional sodium citrate to the amount of 0.011 grams is now added. Finally, distilled water is added in suflcient quantity to bring the volume up to l. cubic centimeter.

The finished solution thus prepared should have a pH value (hydrogen-ion concentration) of about 0.2 and should withstand sterilization. The final solution yields, upon analysis, approximately the following ingredients (per cubic centimeter): h

roteln 0.04 rams Manganese butyrate.. 0.01.: grams 0.052 to 0.06 grams Butyric ucid 0.012 cubic centimeters Benzfl alcohol 0.006 cubic centimeters Distl led water, 13. s. ad 1.000 cubic centimeter The product, as has been indicated, is used by parenteral injection. The average adult dosage is about one cubic centimeter every one or two days in acute cases, and one cubic centimeter every two or three days in chronic cases. Injections may be made in the muscles of the arm, or in muscles elsewhere, or sub-cutaneously. On account of the small dosage, there is customarily no heightened temperature and little discomfort at the site of the injection.

While it is not necessary herein fully to go into the theory of the protective or therapeutic efiect of the fluid here described, it may he indicated that its action isone of intensifying the bodys own powers or resistance, in a nonspecific manner. That is, by placing the proteins in the tissues icy injection, a cellular reaction is caused, which acts upon the vascular system through the vasomotor nerves.

Persuasive evidence hm heretofore been offered that the essential unization is efiected by elements mobilized in the blood serum. These are variously called enzymes, ferments, antibodies, opsonins, or bacteriolysins, but all are one in their antipathy to bacteria, which bacteria they appear to prepare for ingestion by the phagocytes of the blood. Following an injection of the fluid comprising the present invention there is nearly always a multiplication of phagocytes which are attracted in large numbers to the site of a tissue injury or local infection. The phagocytes apparently engulf the bacteria,

- after the bacteria have been acted upon by the body ferments, to digest the bacteria to their lowest degrees and hence to cause their elimi nation.

Injection of the fluid comprising the present invention has been found advantageous in the following, among other cases:

In gynecology, numerous inflammatory conditions, particularly such ,as pelvic infections of women, the injection is advantageous, and is 3 followed by a stimulation particularly of the 'splanchnic organs.

In arthritis, injection is beneficiaLus inchronic atrophic cases with much motion.

In peptic ulcers, the injection is beneficial, though probably not acting through the contra-bacterial manner, but rather by stimulation of vasomotor activity which reduces contractions oi the stomach.

In opthalmology, particularly in the treatmen of conditions such as iritis, corneal infi i tions, sympathetic ophthalmia, and gonorrheal infections of the conjunctiva, injection is beneficial.

' In peripheral vascular disorders, such as thromboangiitis oblitcrans, the injection is also beneficial.

In the treatment of dermatological conditions such as acne vulgaris and some types of. eczema, injections between the layers of the skin, as well as'intramuscular injections, have proved bene-' ficial. 05

In the treatment of gonorrhea, injections are remarkably beneficial for the speed with which they sometimes eliminate the gonococci.

Advanced heart disease, extreme arteriosclerosis, and alcoholism are contra-indications to the use of the present invention. A history of hypersensitivity, such as serum sickness, asthma, or urticaria, should be followed only by cautious treatment. Diabetes (under control) and preg nancy are not contra-indications.

In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

As many changes could be made in carrying out the above compositions and processes without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a. limiting sense.

I claim: I

l. A therapeutical preparation for injection comprising a concentrated solution containing proteins of the therapeutical value corresponding to that of lacteal proteins, and manganese butyrate, both being present in conditions readily assimllalole in the human body, and an alkaline agent and an acid agent adapted, respectively, to hold said proteins and said manganese butyrate in solution through their action to present. a

bufier solution having a pH value of about 6.2.

citrate present in amounts suflicient to hold said proteins in solution, and butyric acid present in amount suflicient to give the solution a pH value of the order of 6.2.

4. A therapeutical preparation for injection having substantially the following composition:

Lacteal proteins 0.04 grams Manganese butyrete 0.015 grams Sodium citrate 0.052 to 0.06 grams 0.012 cubic centimeters enzyl alcohol 0.006 cubic centimeters Water, q. 3. ad 1.000 cubic centimeter M. BECKER. 

